Applications of NMR spectroscopy to systems biochemistry

The past decades of advancements in NMR have made it a very powerful tool for metabolic research. Despite its limitations in sensitivity relative to mass spectrometric techniques, NMR has a number of unparalleled advantages for metabolic studies, most notably the rigor and versatility in structure e...

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Veröffentlicht in:Progress in nuclear magnetic resonance spectroscopy Jg. 92-93; S. 18 - 53
Hauptverfasser: Fan, Teresa W.-M., Lane, Andrew N.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 01.02.2016
Schlagworte:
Animals
Carbon Isotopes - chemistry
Carbon Isotopes - metabolism
Humans
Isotope Labeling
Magnetic Resonance Imaging - methods
Metabolic Networks and Pathways
Mice
Nuclear Magnetic Resonance, Biomolecular - methods
Rats
Systems Biology - methods
Stable isotope resolved metabolomics
Metabolic network and flux
Stable isotope tracers
Hyperpolarization
In vivo NMR
ISSN:0079-6565, 1873-3301
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Zusammenfassung:The past decades of advancements in NMR have made it a very powerful tool for metabolic research. Despite its limitations in sensitivity relative to mass spectrometric techniques, NMR has a number of unparalleled advantages for metabolic studies, most notably the rigor and versatility in structure elucidation, isotope-filtered selection of molecules, and analysis of positional isotopomer distributions in complex mixtures afforded by multinuclear and multidimensional experiments. In addition, NMR has the capacity for spatially selective in vivo imaging and dynamical analysis of metabolism in tissues of living organisms. In conjunction with the use of stable isotope tracers, NMR is a method of choice for exploring the dynamics and compartmentation of metabolic pathways and networks, for which our current understanding is grossly insufficient. In this review, we describe how various direct and isotope-edited 1D and 2D NMR methods can be employed to profile metabolites and their isotopomer distributions by stable isotope-resolved metabolomic (SIRM) analysis. We also highlight the importance of sample preparation methods including rapid cryoquenching, efficient extraction, and chemoselective derivatization to facilitate robust and reproducible NMR-based metabolomic analysis. We further illustrate how NMR has been applied in vitro, ex vivo, or in vivo in various stable isotope tracer-based metabolic studies, to gain systematic and novel metabolic insights in different biological systems, including human subjects. The pathway and network knowledge generated from NMR- and MS-based tracing of isotopically enriched substrates will be invaluable for directing functional analysis of other 'omics data to achieve understanding of regulation of biochemical systems, as demonstrated in a case study. Future developments in NMR technologies and reagents to enhance both detection sensitivity and resolution should further empower NMR in systems biochemical research.
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ISSN:0079-6565
1873-3301
DOI:10.1016/j.pnmrs.2016.01.005